Penicillins and more recently cephalosporins have been recognized for their high degree of antibacterial activity and have been used extensively for the treatment of infectious disease in man. There has been a considerable research effort directed toward the chemical modification of these compounds in search of yet more active beta-lactam antibiotics. Much emphasis has been placed specifically on the variation of the C.sub.6 -acylamino substituent on the penicillin compounds and both the C.sub.7 -acylamino substituent and the C.sub.3 -substituent on the cephem compounds.
Recently R. R. Chauvette and P. A. Pennington reported the use of 3-methylenecephams both in the preparation of 7-amino desacetoxycephalosporanic acid and biologically active derivatives thereof [Journal of Organic Chemistry, 38, 2994 (1973)], and in the preparation of novel 3-methoxy and 3-halo cephems [Journal of the American Chemical Society, 96, 4986 (1974)]. In each case the 3-methylenecepham intermediates were prepared from cephalosporanic acids by first treating the cephalosporanic acids with selected sulfur nucleophiles such as thiourea, thiobenzoic acid, potassium ethyl xanthate or sodium thiosulfate and then reducing the respective product C.sub.3 -(substituted)thiomethyl cephem derivatives with either Raney nickel in aqueous ethanol or zinc in formic acid-dimethylformamide. The demonstrated versatility of the 3-methylenecephams as intermediates to novel cephem antibiotics has prompted a search for alternative procedures for preparing such compounds from readily available, economic starting materials.
This invention relates to certain azetidinone sulfinic acid derivatives and to a process for preparing 3-methylenecepham sulfoxides from such compounds. More particularly this invention relates to the intramolecular cyclization of penicillin sulfoxide derived monocyclic azetidinone-2-sulfinyl chlorides and sulfinic acid, sulfinate ester, thiosulfinate ester, sulfinamide, and sulfinimide derivatives thereof with Friedel-Crafts catalysts or metathetic cation forming agents.